Clinical Stage Research Articles

Uveal melanoma incidence and survival analysis in Portugal between 2013 and 2022

PurposeThis study aims to provide a comprehensive overview of the clinical characteristics and epidemiology of uveal melanoma (UM) in the Portuguese population, evaluated at the National Reference Centre (NRC). MethodsA prospective observational study was conducted, involving patients consecutively diagnosed with UM at the Portuguese NRC between July 2013 and December 2022. The study collected data on demographic and tumour characteristics, clinical staging according to the American Joint Committee on Cancer (AJCC), treatment approaches, local disease control, patient survival, and the occurrence of distant metastases. ResultsThe study included a total of 316 patients, 53.8% female. The mean age at diagnosis was 61.8±14.2 years, and 75.0% of patients presented with symptoms. The mean annual age-adjusted incidence of uveal melanoma in Portugal between 2014 and 2022 was 2.4 cases per million (95% confidence interval [CI]: 2.1–2.8). For choroidal/ciliary body tumours, the overall cumulative survival and distant metastases-free survival (DMFS) rates at 5 years were 84.9% (95% CI: 78.7–91.1) and 79.4% (95%CI: 72.8–86.0), respectively. Notably, higher AJCC stages at presentation, the need for enucleation, and increased tumour thickness were associated with lower DSS and DMFS rates. ConclusionThis study represents the most extensive analysis of UM epidemiology within the Portuguese population. The findings underscore the importance of early diagnosis and treatment in UM, as lower AJCC stages and smaller tumour thickness at diagnosis correlate with improved DSS and DMFS.

Predicting mortality within 1 year of ART initiation in children and adolescents living with HIV in sub-Saharan Africa: a retrospective observational cohort study

Differentiated service delivery (DSD) for children and adolescents living with HIV can improve targeted resource use. We derived a mortality prediction score to guide clinical decision making for children and adolescents living with HIV. Data for this retrospective observational cohort study were evaluated for all children and adolescents living with HIV and initiating antiretroviral therapy (ART); aged 0-19 years; and enrolled at Baylor clinics in Eswatini, Malawi, Lesotho, Tanzania, and Uganda between 2005 and 2020. Data for clinical prediction, including anthropometric values, physical examination, ART, WHO stage, and laboratory tests were captured at ART initiation. Backward stepwise variable selection and logistic regression were performed to develop predictive models for mortality within 1 year of ART initiation. Probabilities of mortality were generated, compared with true outcomes, internally validated, and evaluated against WHO advanced HIV criteria. The study population included 16 958 children and adolescents living with HIV and initiated on ART between May 18, 2005, and Dec 18, 2020. Predictive variables for the most accurate model included: age, CD4 percentage, white blood cell count, haemoglobin concentration, platelet count, and BMI Z score as continuous variables, and WHO clinical stage and oedema, abnormal muscle tone and respiratory distress on examination as categorical variables. The area under the curve (AUC) of the predictive model was 0·851 (95% CI 0·839-0·863) in the training set and 0·822 (0·800-0·845) in the test set, compared with 0·606 (0·595-0·617) for the WHO advanced HIV criteria (p<0·0001). This study evaluated a large, multinational population to derive a mortality prediction tool for children and adolescents living with HIV. The model more accurately predicted clinical outcomes than the WHO advanced HIV criteria and has the potential to improve DSD for children and adolescents living with HIV in high-burden settings. National Institute of Health Fogarty International Center.

Development and Challenges of Cyclic Peptides for Immunomodulation.

Cyclic peptides are polypeptide chains formed by cyclic sequences of amide bonds between protein-derived or non-protein-derived amino acids. Compared to linear peptides, cyclic peptides offer several unique advantages, such as increased stability, stronger affinity, improved selectivity, and reduced toxicity. Cyclic peptide has been proved to have a promising application prospect in the medical field. In addition, this paper mainly describes that cyclic peptides play an important role in anti-cancer, anti-inflammatory, anti-virus, treatment of multiple sclerosis and membranous nephropathy through immunomodulation. In order to know more useful information about cyclic peptides in clinical research and drug application, this paper also summarizes cyclic peptides currently in the clinical trial stage and cyclic peptide drugs approved for marketing in the recent five years. Cyclic peptides have many advantages and great potential in treating various diseases, but there are still many challenges to be solved in the development process of cyclic peptides.

The Enigma That is Rectal Squamous Cell Carcinoma: A Case Series

IntroductionColorectal cancer is the third most common cancer and the third leading cause of cancer deaths in the United States. As rectal squamous cell carcinoma (SCC) is an uncommon colorectal cancer, there is limited data on this clinical entity. We aimed to evaluate the tumor characteristics, treatment, and clinical outcomes of this rare deadly disease. MethodsPathological specimens from 2017 to 2022 at a single National Cancer Institute-designated cancer center were screened for all rectal cases with a diagnosis of SCC. All patients with a primary rectal SCC were included. Patients who had extension to the dentate line or evidence of an anal mass, and those who were treated at an outside institution, were excluded. Demographic, treatment, outcome, and surveillance data was extracted. ResultsThere were 56 specimens identified, nine of which met inclusion criteria. Most patients were White (78%), Hispanic (78%), and female (67%). The average age at diagnosis was 57 y [52-65]. All patients had nodal involvement at the time of clinical staging. All patients were treated with Nigro protocol, with one patient treated with surgery first. The median time of follow-up was 12 mo after initial treatment, 33% had recurrence, with median time to recurrence of 25 mo. Overall, mortality from rectal SCC was 33% at a median time of 37 mo from initial diagnosis. ConclusionsRectal SCC is a colorectal cancer that is not fully understood. Our findings showed that treatment mirrors that of anal SCC, with similar rates of survival to both rectal adenocarcinoma and anal SCC.

Minor (≤ 10%) Ground-Glass Opacity Component in Clinical Stage I Non-Small Cell Lung Cancer: Associations With Pathologic Characteristics and Clinical Outcomes.

Background: The presence of a ground-glass opacity (GGO) component is a favorable prognostic factor in non-small cell lung cancer (NSCLC), although the prognostic impact of a very small GGO component remains poorly investigated. Objective: To investigate the impact of a minor (≤10%) GGO component on the prognosis of clinical stage I NSCLC in comparison with pure-solid nodules. Methods: This retrospective study included 382 patients (mean age, 61 years; 210 men, 172 women) who underwent surgical resection between January 1, 2015 and December 31, 2015 for clinical stage I NSCLC appearing on preoperative chest CT as a nodule with a consolidation-to-tumor (CTR) ratio ≥0.9 and <1.0. Two radiologists independently assigned nodules to a minor-GGO (≥0.9 CTR <1.0) or pure-solid (CTR=1.0) groups. Recurrence-free survival (RFS) and cancer-specific survival (CSS) were assessed by Kaplan-Meier curves and compared between groups using log-rank tests. Cox proportional hazards models were used to assess associations with outcomes. Results: The two radiologists agreed for all nodules' classification into the minor-GGO (n=106) or pure-solid (n=276) groups. The mean CTR of the minor-GGO group was 0.93±0.02 (range, 0.90-0.97). Minor-GGO nodules, in comparison with pure-solid nodules, showed greater solid component diameter (2.68 vs 2.16 cm, p<.001) and total nodule diameter (2.89 vs 2.16 cm, p<.001). The minor-GGO group, in comparison with the pure-solid group, showed lower frequencies of visceral pleural invasion (6.6% vs 17.0%, P=.009), pathologic lymph node involvement (4.7% vs 20.3%, P<.001), and epidermal growth factor mutation (71.6% vs 39.9%; P<.001). The minor-GGO group, in comparison with the pure-solid group, showed better 5-year RFS (83.4% vs 55.0%; P<.001) and better 5-year CSS (92.4% vs 76.4%, P=.004). In multivariable analysis adjusting for patient, imaging, pathologic, and genetic factors, a minor-GGO component was independently associated with a decreased likelihood of recurrence (HR=0.37, P=.001) but not with the likelihood of CSS. Conclusion: Among patients with clinical stage I NSCLC, cancers with a minor-GGO component were associated with a better prognosis versus those with a pure-solid appearance. Clinical Impact: Radiologists encountering predominantly solid nodules on CT should carefully assess images for even a minor-GGO component given the favorable prognosis.

Immunohistochemical Expression and Clinical Significance of WWP1 Protein in Nasopharyngeal Cancer.

Nasopharyngeal carcinoma (NPC) is a common malignant tumor of the head and neck. Its pathogenesis is complicated and needs further investigation. The aim of this study was to investigate the expression and clinical significance of WWP1 in NPC. Bioinformatics approaches were used to evaluate the expression and functions of WWP1 in NPC. WWP1 protein expression was then detected by immunohistochemistry on a tissue microarray in an NPC cohort and its association with clinical features and prognosis was determined. In addition, WWP1 expression was knocked down in NPC cells using RNA interference, and their colony formation and invasion abilities were assessed. A total of 25 genes closely related to WWP1, which may be enriched in different pathways, were filtered out. WWP1 expression was significantly higher in NPC cells than in normal controls. High WWP1 expression was correlated with lymph node metastasis, tumor recurrence, clinical stage and poor prognosis. Knockdown of WWP1 resulted in attenuated proliferation and invasion of NPC cells. The results suggest that WWP1 may serve as a novel biomarker and prognostic factor for NPC and a potential therapeutic target worthy of further investigation.

Computational study on the binding mechanism of allosteric drug TNO155 inhibiting SHP2E76A.

E76A mutations of SHP2 have been reported to associate with genetic developmental diseases and cancers, and TNO155 is one of the effective inhibitors targeted to the allosteric site 1, which has already entered the clinical stage. However, the detailed binding mechanism between them still needs further clarification at micro-atomic level. In this study, the binding mechanism of TNO155 inhibiting SHP2E76A and the superiorities of TNO155 at binding affinity and dynamic interactive behavior with SHP2E76A were probed utilizing a series of computational drug design technologies. The results show that SHP2E76A forms tighter interaction with TNO155 compared to SHP099. SHP2E76A-TNO155 exhibits the largest electrostatic interaction among all complex systems, which can be manifested by the strong hydrogen bond interactions formed by two electrically charged residues, Arg111 and Glu250. Notably, in SHP2E76A-TNO155 system, Asp489 makes an additional substantial beneficial contribution. The E76A mutation brings stronger residue positive correlation and a larger conformation fluctuation between N-CH2 and PTP domains, resulting in tighter binding betweenTNO155and SHP2E76A. This study offers valuable insights for the further design and development of novel SHP2E76A allosteric inhibitors.

Generalizable transcriptome-based tumor malignant level evaluation and molecular subtyping towards precision oncology

In cancer treatment, therapeutic strategies that integrate tumor-specific characteristics (i.e., precision oncology) are widely implemented to provide clinical benefits for cancer patients. Here, through in-depth integration of tumor transcriptome and patients’ prognoses across cancers, we investigated dysregulated and prognosis-associated genes and catalogued such important genes in a cancer type-dependent manner. Utilizing the expression matrices of these genes, we built models to quantitatively evaluate the malignant levels of tumors across cancers, which could add value to the clinical staging system for improved prediction of patients’ survival. Furthermore, we performed a transcriptome-based molecular subtyping on hepatocellular carcinoma, which revealed three subtypes with significantly diversified clinical outcomes, mutation landscapes, immune microenvironment, and dysregulated pathways. As tumor transcriptome was commonly profiled in clinical practice with low experimental complexity and cost, this work proposed easy-to-perform approaches for practical clinical promotion towards better healthcare and precision oncology of cancer patients.

The impact of virtual reality simulation on dental education: A systematic review of learning outcomes and student engagement.

Virtual reality (VR) simulations have been increasingly employed to train dental students prior to clinical practice. According to the literature, blended learning designs in the form of VR simulations can be utilized by both dental students and instructors to provide quality education. They can also save time and improve motor skills before students enter clinical stages. Therefore, this study was designed to review the importance of available VR simulators and their impact on student learning and outcomes. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were followed to review the literature systematically, and different databases such as PubMed, ScienceDirect, Cochrane Library, Scopus, and Google Scholar were searched (up to December 2023) for relevant articles using keywords: "virtual reality," "virtual reality simulators," "virtual reality simulation," and "dental education." The Mixed Methods Appraisal Tool was used to assess the study quality. After a comprehensive literature search, 1477 research articles were identified, of which 16 were included in the present study. In terms of students' learning outcomes, engagement, and optimal approach, a significant improvement was observed compared to conventional training methods, specifically in their knowledge, performance, confidence, and psychomotor skills. The findings suggest that VR simulators enhance the overall learning abilities of dental students and should be regarded as an integral component of the current curriculum. However, it is important to recognize that VR simulators cannot fully substitute traditional training methods; rather, they can effectively complement them.

Counter-intuitive discovery in the formulation of poorly water-soluble drugs: Amorphous small-molecule gels.

Amorphous strategies have been extensively used in improving the dissolution of insoluble drugs for decades due to their high free energy. However, the formation of amorphous small-molecule gels (ASMGs) presents a counter-intuitive discovery that significantly limits their practical application. Recently, ASMGs have garnered attention because of their noncovalent structures, excellent biodegradability, and significant potential in various drug delivery systems in the pharmaceutical field. Hence, a comprehensive review is necessary to contribute to a better understanding of recent advances in ASMGs. This review aimed to introduce the main formation mechanisms, summarize possible influencing factors, generalize unique properties, outline elimination strategies, and discuss clinical application potential with preclinical cases of ASMGs. Moreover, few ASMGs are advanced to clinical stages. Intensive clinical research is needed for further development. We hope that this review can provide more efficient and rational guidance for exploring further clinical applications of ASMGs.

Expression of HER2 in urothelial carcinoma and its significance

Abstract Objectives We explored the expression levels and clinical significance of human epidermal growth factor receptor 2 (HER2) in urothelial carcinoma (UC) tissues. Materials and methods Patient data were reviewed, and 111 paraffin specimens of UC obtained from the Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, from 2020 to 2021 were collected. Immunohistochemistry was used to detect HER2 protein expression in all UC tumor tissues. χ 2 and Fisher exact tests were used to analyze the relationship between HER2 protein expression and clinicopathological data (sex, age, histopathological diagnosis, invasiveness, histopathological grade, maximum tumor diameter, muscle invasion, regional lymph node metastasis, and clinical stage). Results In this study, 92 cases (82.88%) showed HER2 protein expression, and there was a statistically significant difference in the distribution of HER2 positivity (immunohistochemistry 2+ and 3+) according to the pathological grades of UC (p = .021). Human epidermal growth factor receptor 2 positivity was not associated with sex, age, histopathological diagnosis, invasiveness, maximum tumor diameter, muscle invasion, regional lymph node metastasis, or clinical stage (all p &lt; .05). Conclusions HER2 protein is highly expressed in UC, and its expression may be closely related to the high pathological grade of UC.

Clinical and histopathological parameters in transrectal ultrasound-guided biopsies associated with tumor upgrading after radical prostatectomy: A comparative analysis of risk groups.

Thanks to technological advances, prostate cancer (PCa) can be diagnosed at a younger age. It is known that most of these patients are in the low-intermediate risk group, and the histological grade of the tumor increases in half of those undergoing radical prostatectomy (Rp) compared to their diagnostic biopsies. This is especially important in terms of active surveillance (AS) and/or the timely evaluation of curative treatment options in patients diagnosed at an early age. Our aim was to investigate clinical and histopathological parameters that may be associated with an increase in the histological grade of the tumor in patients with acinar adenocarcinoma who were diagnosed by transrectal ultrasound-guided biopsy (TRUS-Bx) and underwent Rp. A total of 205 patients with classical acinar adenocarcinoma diagnosed by TRUS-Bx without metastasis and who underwent Rp were grouped according to the D'Amico risk classification. Age at diagnosis, serum prostate-specific antigen (PSA), PSA density, prostate volume, Prostate Imaging Reporting and Data System (PI-RADS) score, clinical stage, Gleason Grade Group (GGG), high-grade intraepithelial neoplasia in tumor-free cores (HGPIN) (single and ≥2 cores), perineural invasion (PNI), and lymphovascular invasion (LVI) was obtained. Additionally, GGG, pathological stage, lymph node metastasis, surgical margin positivity, and tumor volume obtained from Rp were evaluated. Comparisons were made between the case groups in which the tumor grade increased and remained the same, in terms of age, serum PSA, PSA density, HGPIN in tumor-free cores (single and ≥2 cores), PNI, and LVI in all biopsies (with or without tumors), as well as risk groups. In addition, the relationships of HGPIN in tumor-free cores (single and ≥2 cores), PNI, and LVI on TRUS-Bx with age, serum PSA and PSA density, tumor volume, surgical margin positivity, pathological stage, lymph node metastasis, and risk groups were examined separately. Of the patients, 72 (35.1%) were in the low-risk group, 95 (46.3%) in the intermediate-risk group, and 38 (18.5%) in the high-risk group. Most of the patients with an increased histological grade (n = 38, 48.1%) were in the low-risk group (p < 0.05) and had an advanced median age. HGPIN in single and ≥2 tumor-free cores and PNI were more common in these patients (p < 0.01, p < 0.001, and p < 0.05, respectively). According to the multivariable analysis, advanced age (odds ratio [OR]: 1.087, 95% confidence interval [CI]: 1.029-1.148, p < 0.05), high serum PSA (OR: 1.047, 95% CI: 1.006-1.090, p < 0.05), HGPIN in ≥2 tumor-free cores (OR: 6.346, 95% CI: 3.136-12.912, p < 0.001), and PNI (OR: 3.138, 95% CI: 1.179-8.356, p < 0.05) were independent risk factors for a tumor upgrade. Furthermore, being in the low-risk group was an independent risk factor when compared to the intermediate- and high-risk groups (OR: 0.187, 95% CI: 0.080-0.437, p < 0.001 and OR: 0.054, 95% CI: 0.013-0.230, p < 0.001, respectively). The HGPIN diagnosis was more common in the low- and intermediate-risk groups. Advanced age at diagnosis, high serum PSA and PSA density values were associated with PNI on TRUS-Bx. High serum PSA and PSA density values were associated with LVI on TRUS-Bx. Surgical margin positivity was higher in cases with PNI and LVI detected by TRUS-Bx. HGPIN in ≥2 tumor-free cores, PNI, and LVI on TRUS-Bx were associated with a higher rate of lymph node metastases. In patients diagnosed with acinar adenocarcinoma, the presence of HGPIN even in a single tumor-free core on TRUS-Bx was found to be significant in terms of showing an increase in the histological tumor grade in Rp. The diagnosis of HGPIN in ≥2 tumor-free cores on TRUS-Bx was determined as an independent risk factor for an increased Gleason score after Rp. Furthermore, an advanced age, a high serum PSA value, being in the low-risk group, and the presence of PNI were associated with a tumor upgrade. HGPIN in ≥2 tumor-free cores, PNI, and LVI were also associated with lymph node metastasis. Therefore, the diagnosis of HGPIN should be signed out on pathological reports.

Single-cell RNA-binding protein pattern-mediated molecular subtypes depict the hallmarks of the tumor microenvironment in bladder urothelial carcinoma

Abstract Objectives Bladder carcinoma (BC) is a common malignancy of the urinary tract. As a new hallmark of cancer for drug therapy, RNA-binding proteins (RBPs) are key regulatory factors in alternative splicing events. This work is to uncover the relationship between BC and RBP in order to find drug targets in BC. Methods In this work, data from single-cell RNA-seq GSE1355337, PRJNA662018, and the TCGA-Bladder urothelial carcinoma (BLCA) cohorts are integrated to identify their relationships. A scoring system is constructed according to RBPs gene expression and patients’ survival. A network is constructed to analyze the alternative splicing events and RBP genes. Results A scoring system identified 321 RBPs significantly associated with the prognosis of patients. Subsequent typing of these RBP genes in two single-cell datasets demonstrated that most of the RBP genes had variable copy numbers. Three RBP clusters were identified. Using RBP genes as a signature in BC epithelial cells allows for differentiation between different grades of BC samples. The novel RBP genes-based subtype system reflects BC clinical staging. Notably, CellChat analysis revealed that the RBP genes-associated cell subtypes of T cells had extensive interactions with epithelial cells. Further analysis showed that the ligand-receptor pair MIF-CXCR4 mediated the communication between RBP-associated subtypes of BC epithelial cells and T cells. Conclusions Taken together, RBP genes are associated with BC progress and offer new indicators for precision medicine in BC.

Prognostic implication of methylation-based circulating tumor DNA detection prior to surgery in stage I non-small cell lung cancer

BackgroundCirculating tumor DNA (ctDNA) positivity at diagnosis, which is associated with worse outcomes in multiple solid tumors including stage I–III non-small cell lung cancer (NSCLC), may have utility to guide (neo)adjuvant therapy. MethodsIn this retrospective study, 260 patients with clinical stage I NSCLC (180 adenocarcinoma, 80 squamous cell carcinoma) were allocated (2:1) to high- and low-risk groups based on relapse versus disease-free status ≤5 years post-surgery. We evaluated the association of preoperative ctDNA detection by a plasma-only targeted methylation-based multi-cancer early detection (MCED) test with NSCLC relapse ≤5 years post-surgery in the overall population, followed by histology-specific subgroup analyses. ResultsAcross clinical stage I patients, preoperative ctDNA detection did not associate with relapse within 5 years post-surgery. Sub-analyses confined to lung adenocarcinoma suggested a histology-specific association between ctDNA detection and outcome. In this group, ctDNA positivity tended to associate with relapse within 2 years, suggesting prognostic implications of MCED test positivity may be histology- and time-dependent in stage I NSCLC. Preoperative ctDNA detection was associated with upstaging of clinical stage I to pathological stage II–III NSCLC. ConclusionsOur findings suggest preoperative ctDNA detection in patients with resectable clinical stage I NSCLC using MCED, a pan-cancer screening test developed for use in an asymptomatic population, has no detectable prognostic value for relapse ≤5 years post-surgery. MCED detection may be associated with early adenocarcinoma relapse and increased pathological upstaging rates in stage I NSCLC. However, given the exploratory nature of these findings, independent validation is required.

Determining the optimal distal resection margin in rectal cancer patients by imaging of large pathological sections: An experimental study.

To determine the distal resection margin in sphincter-sparing surgery in patients with low rectal cancer based on imaging of large pathological sections. Patients who underwent sphincter-sparing surgery for ultralow rectal cancer at Guangxi Medical University Cancer Hospital within the period from January 2016 to March 2022 were tracked and observed. The clinical and pathological data of the patients were collected and analyzed. The EVOS fluorescence automatic cell imaging system was used for imaging large pathological sections. Follow-up patient data were acquired mainly by sending the patients letters and contacting them via phone calls, and during outpatient visits. A total of 46 patients (25 males, 21 females) aged 27 to 86 years participated in the present study. Regarding clinical staging, there were 9, 10, 16, and 10 cases with stages I, II, III, and IV low rectal cancer, respectively. The surgical time was 273.82 ± 111.51 minutes, the blood loss was 123.78 ± 150.91 mL, the postoperative exhaust time was 3.67 ± 1.85 days, and the postoperative discharge time was 10.36 ± 5.41 days. There were 8 patients with complications, including 3 cases of pulmonary infection, 2 cases of intestinal obstruction, one case of pleural effusion, and one case of stoma necrosis. The longest and shortest distal resection margins (distances between the cutting edges and the tumor edges) were 3 cm and 1 cm, respectively. The minimum length of the extension areas of the tumor lesions in the 46 images of large pathological sections was 0.1 mm, and the maximum length was 15 mm. Among the tumor lesions, 91.30% (42/46) had an extension area length of ≤5 mm, and 97.83% (45/46) had an extension area length of ≤10 mm. The length of the extension zone was not related to clinical pathological parameters (P > .05). In the vast majority of cases, the distal resection margin was at least 1 cm; thus, "No Evidence of Disease" could have been achieved. Additional high-powered randomized trials are needed to confirm the results of the present study.

Death associated protein kinase 1 predicts the prognosis and the immunotherapy response of various cancers.

Death Associated Protein Kinase 1 (DAPK1) is a calcium/calmodulin-dependent serine/threonine kinase, which has been reported to be a tumor suppressor with unbalanced expression in various tissues. However, its function in tumor immunotherapy is still unclear. The online GEPIA2 database was used to support TCGA results. We explored the DAPK1 pan-cancer genomic alteration analysis using the cBioPortal web tool. The Human Protein Atlas (HPA) was employed to mine DAPK1 protein information. We verified the expression of DAPK1 in lung adenocarcinoma samples using RT-qPCR. Subsequently, the relationship between the expression of DAPK1 and the clinical stage was analyzed. We used TIMER2.0 as the primary platform for studying DAPK1-related immune cell infiltration. Associations between DAPK1 and immunotherapy biomarkers were analyzed using Spearman correlation analysis. TMB and MSI expression was also examined. Finally, we used Kaplan-Meier Plots to evaluate the relationship between DAPK1 expression and the efficacy of immunotherapy. DAPK1 is aberrantly expressed in most cancer types and has prognostic power in various cancers. Gene mutation was the most common DAPK1 alteration across pan-cancers. The DAPK1 protein was mainly localized to tumor cell centrosomes. DAPK1 was also significantly associated with immune-activated hallmarks, immune cell infiltration, and the expression of immunomodulators. Notably, DAPK1 can also significantly predict responses to anti-PD1 and anti-CTLA-4 therapy in cancer patients. Our findings suggest that DAPK1 may not only be an effective prognostic factor in cancer patients but may also function as a promising predictive immunotherapy biomarker for cancer patients treated with immune checkpoint inhibitors.

Minorities Face Delays to Pancreatic Cancer Treatment Regardless of Diagnosis Setting.

Our analysis was designed to characterize the demographics and disparities between the diagnosis of pancreas cancer during emergency presentation (EP) and the outpatient setting (OP) and to see the impact of our institutions pancreatic multidisciplinary clinic (PMDC) on these disparities. Institutional review board-approved retrospective review of our institutional cancer registry and PMDC databases identified patients diagnosed/treated for pancreatic ductal adenocarcinoma between 2014 and 2022. Chi-square tests were used for categorical variables, and one-way ANOVA with a Bonferroni correction was used for continuous variables. Statistical significance was set at p < 0.05. A total of 286 patients met inclusion criteria. Eighty-nine patients (31.1%) were underrepresented minorities (URM). Fifty-seven (64.0%) URMs presented during an EP versus 100 (50.8%) non-URMs (p = 0.037). Forty-one (46.1%) URMs were reviewed at PMDC versus 71 (36.0%) non-URMs (p = 0.10). No differences in clinical and pathologic stage between the cohorts (p = 0.28) were present. URMs took 22 days longer on average to receive treatment (66.5 days vs. 44.8 days, p = 0.003) in the EP cohort and 18 days longer in OP cohort (58.0 days vs. 40.5 days, p < 0.001) compared with non-URMs. Pancreatic Multidisciplinary Clinic enrollment in EP cohort eliminated the difference in time to treatment between cohorts (48.3 days vs. 37.0 days; p = 0.151). Underrepresented minorities were more likely to be diagnosed via EP and showed delayed times to treatment compared with non-URM counterparts. Our PMDC alleviated some of these observed disparities. Future studies are required to elucidate the specific factors that resulted in these findings and to identify solutions.

Analysis of the pharmacokinetics and efficacy of RBD1016 – A GalNAc-siRNA targeting Hepatitis B Virus X gene using semi-mechanistic PK/PD model

Small interference RNA (siRNA) is a class of short double-stranded RNA molecules that cause mRNA degradation through an RNA interference mechanism and is a promising therapeutic modality. RBD1016 is a siRNA drug in clinical development for the treatment of chronic Hepatitis B Virus (HBV) infection, which contains a conjugated with N-acetylglucosamine moiety that can facilitate its hepatic delivery. We aimed to construct a semi-mechanistic model of RBD1016 in pre-clinical animals, to elucidate the pharmacokinetic/pharmacodynamic (PK/PD) profiles in mice and PK profiles in monkeys, which can lay the foundation for potential future translation of RBD1016 PK and PD from the pre-clinical stage to the clinic stage. The proposed semi-mechanistic PK/PD model fitted PK and PD data in HBV transgenic mice well and described plasma and liver concentrations in the monkeys well. The simulation results showed that our model has a reasonable predictive ability for Hepatitis B surface antigen (HBsAg) levels after multiple dosing in mice. Further PK and PD data for RBD1016, including clinical data, will assist in refining the model presented here. Our current effort focused on model building for RBD1016, we anticipate that the model could apply to other GalNAc-siRNA drugs.

Robotic Surgery for Head and Neck Tumors: What are the Current Applications?

The journey from radical treatments to the precision of robotic surgery underscores a commitment to innovation and patient-centered care in the field of head and neck oncology. This article provides a comprehensive overview that not only informs but also stimulates ongoing discourse and investigation into the optimization of patient care through robotic surgery. The literature on current robotic applications within head and neck region was systematically reviewed. Thirty-four studies with a total of 1835 patients undergoing robotic surgery in head and neck region were included. Clinical staging, histological types, operative duration, postoperative complications, functional recovery and survival outcomes were compared and evaluated. Clinical outcomes have shown promising results and thus the indication on the robotic usage has no longer been limited to oropharyngeal region but from skull base to neck dissection. The latest advancement in robotic surgery further refines the capabilities of surgeons into previously difficult-to-access head and neck regions and heralds a new era of surgical treatment for head and neck oncology.

Correlation of Clinical and Pathological TNM Staging With Histopathological Grading in Oral Squamous Cell Carcinoma

Correlation of Clinical and Pathological TNM Staging With Histopathological Grading in Oral Squamous Cell Carcinoma